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Objectives Taniborbactam is a boronate-based β-lactamase inhibitor in clinical development in combination with cefepime. Methods Cefepime–taniborbactam and comparator broth microdilution MICs were determined for patient isolates of Enterobacterales (n  = 20 725) and Pseudomonas aeruginosa (n  = 7919) collected in 59 countries from 2018 to 2022. Taniborbactam was tested at a fixed concentration of 4 mg/L. Isolates with cefepime–taniborbactam MICs   ≥   16 mg/L underwent WGS. β-Lactamase genes were identified in additional meropenem-resistant isolates by PCR/Sanger sequencing. Results Taniborbactam reduced the cefepime MIC90 value for all Enterobacterales from >16 to 0.25 mg/L (>64-fold). At ≤16 mg/L, cefepime–taniborbactam inhibited 99.5% of all Enterobacterales isolates; >95% of isolates with MDR and ceftolozane–tazobactam-resistant phenotypes;  ≥ 89% of isolates with meropenem-resistant and difficult-to-treat-resistant (DTR) phenotypes; >80% of isolates with meropenem–vaborbactam-resistant and ceftazidime–avibactam-resistant phenotypes; 100% of KPC-positive, 99% of OXA-48-like-positive, 99% of ESBL-positive, 97% of acquired AmpC-positive, 95% of VIM-positive and 76% of NDM-positive isolates. Against P. aeruginosa , taniborbactam reduced the cefepime MIC90 value from 32 to 8 mg/L (4-fold). At ≤16 mg/L, cefepime–taniborbactam inhibited 96.5% of all P. aeruginosa isolates; 85% of meropenem-resistant phenotype isolates; 80% of isolates with MDR and meropenem–vaborbactam-resistant phenotypes; >70% of isolates with DTR, ceftazidime–avibactam-resistant and ceftolozane–tazobactam-resistant phenotypes; and 82% of VIM-positive isolates. Multiple potential mechanisms of resistance, including carriage of IMP, or alterations in PBP3 (ftsI), porins (decreased permeability) and efflux (up-regulation) were present in most isolates with cefepime–taniborbactam MICs   ≥   16 mg/L. Conclusions Cefepime–taniborbactam exhibited potent in vitro activity against Enterobacterales and P. aeruginosa , and inhibited most carbapenem-resistant isolates, including those carrying serine carbapenemases or NDM/VIM MBLs. [ABSTRACT FROM AUTHOR]

Background: We report results from the national CLEAR (Canadian Leadership on Antimicrobial Real-Life Usage) registry on the usage of ceftolozane/tazobactam in Canada from 2022 to 2024. Research design and methods: The authors reviewed the final data using the national ethics approved CLEAR study. Thereafter, the literature is surveyed regarding the usage of ceftolozane/tazobactam to treat patients with HABP and VABP via PubMed (up to May 2024). Results: Ceftolozane/tazobactam was primarily used as directed therapy to treat HABP and VABP caused by Pseudomonas aeruginosa. It was primarily used alone, or in combination with another agent, to treat resistant and multidrug-resistant (MDR) P. aeruginosa infections. Despite primarily being used to treat severely ill patients in intensive care units, its use was associated with relatively high microbiological/clinical cure rates, along with an excellent safety profile. Several reports attest to the microbiological/clinical efficacy and safety of using ceftolozane/tazobactam to treat HABP and VABP. Conclusions: In Canada, ceftolozane/tazobactam is primarily used as directed therapy alone, or in combination, to treat MDR P. aeruginosa infections. Though mostly used to treat severely ill patients in the ICU, ceftolozane/tazobactam use in HABP and VABP is associated with relatively high microbiological/clinical cure rates and an excellent safety profile. [ABSTRACT FROM AUTHOR]

Background Lower respiratory infections and invasive disease caused by Streptococcus pneumoniae serotype 3 remain major clinical challenges around the world, despite widespread availability of updated vaccines. Methods As part of CANWARD, antimicrobial susceptibility testing and serotyping were performed on all S. pneumoniae isolates from 2007 to 2021. A subset of 226/264 (85.6%) serotype 3 isolates were selected for WGS to determine sequence type (ST)/clonal cluster (CC) and correspondence of antimicrobial resistance determinants (erm , mefAE , tetM , cat , folA , folP) with resistance phenotype. Results Of the 3,039 S. pneumoniae isolates obtained from 2007 to 2021, 8.7% (n  = 264) were serotype 3, with 64.0% of respiratory origin and 36.0% from blood. Of 226 sequenced serotype 3 isolates, 184 (81.4%) were ST180 (GPSC12). The proportion of ST8561 (single locus variant of ST180) increased from 7.2% to 16.6% during the study period. An increasing proportion of serotype 3 isolates had phenotypic resistance (P  = 0.0007) and genetic resistance determinants (P  = 0.004), comparing 2017–21 to 2007–11, largely due to a recently expanded ST180 clade with cat , tetM and mef determinants. Conclusions S. pneumoniae serotype 3 from GPSC12 continues to dominate throughout Canada, with an increase in the proportion of ST8561. The proportion of serotype 3 isolates that are phenotypically resistant and with genetic resistance determinants is increasing over time, reflecting a global increase in GPSC12 genotypes with known resistance determinants. Phylogenomic characterization of isolates collected over time and from around the world may facilitate improved treatment and enhanced prevention strategies, including new vaccines with activity against S. pneumoniae serotype 3. [ABSTRACT FROM AUTHOR]

Background: We report the final results of the clinical usage of ceftobiprole in patients in Canada from data in the national CLEAR (Canadian Le adership on Antimicrobial Real-Life Usage) registry. Research design and methods: The authors review the final data using the national ethics approved CLEAR study. Thereafter, the literature is surveyed regarding the usage of ceftobiprole to treat patients with infectious diseases via PubMed (up to March 2024). Results: In Canada, ceftobiprole is primarily used as directed therapy to treat a variety of severe infections caused by MRSA. It is primarily used in patients failing previous antimicrobials, is frequently added to daptomycin and/or vancomycin with high microbiological and clinical cure rates, along with an excellent safety profile. Several reports attest to the microbiological/clinical efficacy and safety of ceftobiprole. Ceftobiprole is also reported to be used empirically in select patients with community-acquired bacterial pneumonia (CABP), as well as hospital-acquired bacterial pneumonia (HABP). Conclusions: In Canada, ceftobiprole is used mostly as directed therapy to treat a variety of severe infections caused by MRSA, in patients failing previous antimicrobials. It is frequently added to, and thus used in combination with daptomycin and/or vancomycin with high microbiological/clinical cure rates, and an excellent safety profile. [ABSTRACT FROM AUTHOR]